Toluene exposure

Hillefors-Berglund M, Liu Y, von Euler G Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen. Toxicology 77 223-232, 1993... 

Though distillable at considerably reduced pressure, phenyl azide explodes when heated at ambient pressure, and occasionally at lower pressures [1]. The energy of decomposition has been determined (130-260°C) as 1.36 kJ/g by DSC, and Tait24 was determined as 87°C by adiabatic Dewar tests, with an apparent energy of activation of 119 kJ/mol [2], It is best stored as a 3M solution in toluene. Exposure to heavy metals should be avoided [3],... 

In a study where both peripheral and central nervous system effects were measured in rats co-exposed to u-hexane and toluene (Pryor and Rebert 1992), toluene exposure at 1,400 ppm for 14 hours a day for 9 weeks prevented the peripheral neurotoxicity (decreased grip strength and nerve conduction velocities) caused by exposure to 4,000 ppm 77-hcxanc alone. There was no reciprocal action of 77-hexane on the motor syndrome (shortened and widened gait and widened landing foot splay) and hearing loss caused by toluene. Brainstem auditory response amplitudes were decreased by 77-hcxanc, co-exposure to toluene did not block this effect. 

Toluene exposure does not result in the hematopoietic effects caused by benzene. The myelotoxic effects previously attributed to toluene are judged by more recent investigations to be the result of concurrent exposure to benzene present as a contaminant in toluene solutions. Most of the toluene absorbed from inhalation is metabolized to benzoic acid, conjugated with glycine in the liver to form hippuric acid, and excreted in the urine. The average amount of hippuric acid excreted in the urine by persons not exposed to toluene is approximately 0.7-1.0 g/1 of urine. ... 

A chronic inhalation study found no evidence of carcinogenic activity in rats exposed at concentrations of 600 ppm or 12 00 ppm for 2 years, or in mice exposed at 120, 600, or 1200 ppm for the same duration.Epidemiological findings of various cancer (stomach, lung, and colorectal) increases with toluene exposure are not strong enough to conclude an association because of multiple exposure circumstances and weak consistency of findings."... 

Samples of your urine can be tested for the presence of cresols, although this test is not routinely available in hospitals and clinics. This test will not tell you whether or not you will have any adverse health effects. The urine sample would have to be taken within 1 day of your exposure to be valid. Because cresols occur naturally in people, ant at levels that very from one individual to the next, results from tests for cresol exposure should be compared to values obtained from the same individual either before exposure or several days after exposure. Small changes might be caused by variation in daily diet. You should also be aware that an increased presence of cresols in the urine could indicate exposure to toluene, a related compound, rather than cresols. However, toluene exposure would also result in elevated urinary levels of hippuric acid cresol exposure would not. 

Biomarkers of Exposure and Effect. No biomarkers of exposure to cresols have been identified. In fact, even the cresols themselves cannot be considered specific biomarkers for cresol exposure because they are also formed as breakdown products of toluene and tyrosine. However, if toluene exposure could be ruled out, then a high level of cresols or metabolites in the blood or urine would strongly suggest cresol exposure. Distinguishing biomarkers of exposure to cresols would enable early detection of cresol exposure and provide the opportunity for early treatment. One possibility that can be further investigated is Heinz body formation in the blood of exposed humans (Chan et al. 1971 Cote et al. 1984). 

Numerous methods for the determination of o-, m-, and p-cresol in urine have appeared in the literature, but none have been standardized. Cresol in urine is often measured to determine exposure to toluene or other aromatic compounds, of which cresol is a metabolite. The analytical methods summarized in Table 6-1 are sufficiently sensitive to detect the individual isomers of cresol at a concentration that may cause concern for human health. Humans normally excrete 16-29 mg of p-cresol daily as a result of the breakdown of tyrosine (Needham et al. 1984), and o-cresol is an indicator of toluene exposure (DeRosa et al. 1987). 

Toluene (methylbenzene) does not possess the myelotoxic properties of benzene, nor has it been associated with leukemia. It is, however, a central nervous system depressant and a skin and eye irritant. It is also fetotoxic. See Table 56-1 for the TLVs. Exposure to 800 ppm can lead to severe fatigue and ataxia 10,000 ppm can produce rapid loss of consciousness. Chronic effects of long-term toluene exposure are unclear because human studies indicating behavioral effects usually concern exposures to several solvents. In limited occupational studies, however, metabolic interactions and modification of toluene s effects have not been observed in workers also exposed to other solvents. Less refined grades of toluene contain benzene. 

During inhalation exposure of human volunteers to low levels of toluene (200-300 mg/mty, approximately 50% of the inhaled toluene was absorbed (Lbf et al., 1993). Such studies at low toluene exposure are complicated by the presence of toluene from other sources, in blood or in urine (Pierce et al., 1996). If the deuterated [ Hgjtoluene is used for exposure, this problem is avoided [but an isotope effect may reduce the rate of the metabolism of deuterated toluene compared to normal toluene, possibly by 30-50%]. When toluene is administered orally, it is virtually completely absorbed from the gastrointestinal tract (Baelum et al., 1993). 

Several authors have pointed out that the urinary excretion of hippurate is a poor indicator of exposure to toluene at 200 ppm [760 mg/m ] or lower (Jonai Sato, 1988 Too et al., 1991 Pierce et al., 1996). Therefore, data on ethnic differences in hippurate or cresol excretion in urine at these low exposure levels (e.g., Inoue et al., 1988) are of doubtful significance. Toluene level in expired air may be a more reliable parameter (Foo et al., 1991). Although at the level of the individual, data on urinary hippurate cannot be reliably used to estimate low toluene exposures, they can be used at the group level to establish whether at a certain location the toluene exposure remained below a particular threshold (Lauwerys, 1983). 

In guinea-pigs, the presence of surfactants (e.g., Triton X-45 or X-100) decreased the skin absorption of toluene (Boman et al., 1989). Intermittent skin exposure (for 1 min, every 30 min, repeated eight times) resulted in a blood toluene area-under-the-curve (AUC) of 16% compared to that seen with continuous toluene exposure (Boman et al., 1995), with little change in the extent of absorption at each repeated exposure, indicating that the skin did not become more permeable w ith repeated exposure. 

Increased frequency of subjective symptoms, but no indication of hepatic or renal damage, was observed among 452 toluene-exposed workers, when the actual toluene exposure was 24.7 4.43 ppm [93 17 mg/m ] (geometric mean standard deviation) and toluene represented more than 90% of the airborne solvent vapours (Ukai et al., 1993). Similarly, no clinical chemical indication of hepatic damage was observed among 153 workers with exposure to toluene of 1-60 ppm [3.8-230 mg/m ] during workdays for two to five years (Wang et al., 1996). 

Trinitro Toluene Exposure to dust may irritate mucous membranes permissible concn in air 1.5 mg/m3... 

A disadvantage to measuring toluene exposure by hippuric acid is the production of this metabolite from natural sources, and the determination of toluylmercapturic acid is now favored as a biomarker of toluene exposure.10 An interesting sidelight is that dietary habits can cause uncertainties in the measurement of xenobiotic metabolites. An example of this is the measurement of worker exposure to 3-chloropropene by the production of allylmercapturic acid.11 This metabolite is also produced by garlic, and garlic consumption by workers was found to be a confounding factor in the method. Thiocyanate monitored as evidence of exposure to cyanide is increased markedly by the consumption of cooked cassava. 

Angerer, J., Schildbach, M., and Kramer, A., S-toluylmercapturic acid in the urine of workers exposed to toluene a new biomarker for toluene exposure, Arch. Toxicol., 72, 119-123, 1998. 

Boewer, C., Enderlein, G., Wollgast, U., Nawka, S., Palowski, H., Bleiber, R. Epidemiological study on the hepatotoxicity of occupational toluene exposure. Int. Arch. Occup. Environ. Health 1988 60 181-186... 

Baelum J, Andersen I, Lundqvist GR, et al. 1985. Response of solvent-exposed printers and unexposed controls to six-hour toluene exposure. Scand J Work Environ Health 11 271-280. 

Hseih GC, Sharma RP, Parker RD. 1989. Immunological evaluation of toluene exposure via drinking water in mice. Environ Res 49 93-103. 

KeU (USA) 1998 Parts washing operation Toluene Exposure estimate range (mg/m )... 

Hawkins, N. C., and Evans, J. S. (1989). Subjective estimation of toluene exposures A calibration study of industrial hygienists. Appl Ind Hyg 4, 61-68. 

Eller N, Netterstrom B, Laursen P Risk of chronic effects on the central nervous system at low toluene exposure. Occup Med 49 389-395, 1999 Foo SC, Jeyaratnam J, Koh D Chronic neurobehavioral effects of toluene. British Journal of Industrial Medicine 47 480-484, 1990 Foo SC, Ngim CH, Salleh I, et al Neurobehavioral effects in occupational chemical exposure. Environ Res 60 267-273, 1993... 

Benignus, V.A., W.K. Boyes, and P.J. Bushnell. 1998. A dosimetric analysis of behavioral effects of acute toluene exposure in rats and humans. Toxicol. Sci. 43 (2) 186-195. 

---